{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:08:30Z","timestamp":1791472110016,"version":"4.3.4"},"reference-count":43,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2013,5,15]]},"abstract":"<jats:p>Fibroblast growth factor 19 (FGF19) is proposed to be a negative feedback regulator of hepatic bile acid (BA) synthesis. We aimed to clarify the distribution of FGF19 expression in human intestine and to investigate induction in a novel explant system. Ileal and colonic mucosal biopsies were obtained at endoscopy and analyzed for FGF19 transcript expression. Primary explants were incubated with physiological concentrations of various BA for up to 6 h, and expression of FGF19 and other genes was determined. FGF19 transcripts were detected in ileum but were unquantifiable in colon. No loss of FGF19 mRNA occurred as a consequence of the explant system. Ileal FGF19 transcript expression was induced 350-fold by 50 \u03bcM chenodeoxycholate (CDCA, n = 24, P &lt; 0.0001) and 161-fold by 50 \u03bcM glycochenodeoxycholate (GCDCA, n = 12, P = 0.0005). The responses of other genes to CDCA or GCDCA (50 \u03bcM) were smaller: median increases of ileal bile acid binding protein, organic solute transporter-\u03b1 and -\u03b2, and short heterodimer partner were 2.4- to 4.0-fold; apical membrane sodium bile acid transporter and farnesoid X receptor (FXR) showed little change. The EC50 for FGF19 transcript induction by CDCA was 20 \u03bcM. FGF19 protein concentrations were significantly higher in the culture fluid from BA-stimulated explants. FGF19 induction with cholate was 81% of that found with CDCA, but deoxycholate (40%) and lithocholate (4%) were significantly less potent. The synthetic FXR agonist obeticholic acid was much more potent than CDCA with a 70-fold FGF19 stimulation at 1 \u03bcM. We concluded that FGF19 expression in human ileum is very highly responsive to BA. Changes in FGF19 induction are a potential mechanism involved in disorders of BA homeostasis.<\/jats:p>","DOI":"10.1152\/ajpgi.00398.2012","type":"journal-article","created":{"date-parts":[[2013,3,22]],"date-time":"2013-03-22T02:09:42Z","timestamp":1363918182000},"page":"G940-G948","source":"Crossref","is-referenced-by-count":101,"title":["Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids"],"prefix":"10.1152","volume":"304","author":[{"given":"Justine H.","family":"Zhang","sequence":"first","affiliation":[{"name":"Section of Hepatology and Gastroenterology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Nolan","sequence":"additional","affiliation":[{"name":"Section of Hepatology and Gastroenterology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Kennie","sequence":"additional","affiliation":[{"name":"Section of Hepatology and Gastroenterology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Section of Hepatology and Gastroenterology, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Dew","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry, King's College Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Obstetric Medicine, Imperial College London and Imperial College Healthcare, London;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Williamson","sequence":"additional","affiliation":[{"name":"Obstetric Medicine, Imperial College London and Imperial College Healthcare, London;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian R. 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